PROJECT SUMMARY Alcohol Use Disorder (AUD) is prevalent, devastating, and difficult to treat. High relapse rates are likely due to factors that affect neural circuits that govern craving and cognitive control. There is growing interest in the utilization of prefrontal cortex repetitive transcranial magnetic stimulation (TMS) as a novel, non-invasive, non- pharmacologic approach to decreasing craving among individuals with alcohol use disorder (AUD). At this early stage of development, however, it is unclear if the best TMS strategy is to (1) attenuate activity in the medial prefrontal cortex (mPFC, which is involved in craving), or (2) amplify activity in the dorsolateral prefrontal cortex (dlPFC, which is involved in cognitive control). Several laboratories have demonstrated that a single session of 10 Hz TMS over the dlPFC leads to a decrease in craving for alcohol, nicotine, and cocaine. We have demonstrated that a single session of continuous theta burst (cTBS) TMS over the mPFC can also decrease craving, as well as the brain response to drug cues in cocaine users and alcohol users. The overarching goal of this proposal is to determine which of these brain stimulation strategies is more effective in decreasing functional activity (measured by BOLD signal) in limbic regions involved in alcohol craving (Aim 1), and decreasing self-reported craving (Aim 2). This will be achieved through a double-blind, sham-TMS controlled within-subject crossover study of individuals with AUD. Using functional MRI, the neural response to alcohol-cues (a task identical to that used in Research Project #2- Anton/Schacht) will be measured within 10 minutes after the participant receives a dose of continuous theta burst TMS to the mPFC, 10 Hz TMS to the dlPFC, or sham rTMS. Additionally, the effects of these TMS strategies on cortical neurochemistry will be measured using magnetic resonance spectroscopy (exploratory Aim 3), enabling us to relate the outcomes of these aims with complementary neurochemical information. The outcomes of this project will provide an evidence-based foundation for cortical target selection in future clinical trials of TMS as an innovative treatment strategy for individuals with AUD.